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We investigated the relationship between contextual exposures and cognitive outcomes, independent of and in interaction with polygenic risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Using the Multi\u2010Ethnic Study of Atherosclerosis (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a05687), we assessed the associations of contextual determinants representing the social, chemical, and built environment with incident dementia and late\u2010life cognition using proportional hazards regression and generalized estimating equation models, then evaluated their joint effects stratified by genetic risk via Bayesian kernel machine regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Neighborhood disadvantage was associated with higher dementia risk and poorer cognitive scores after adjusting for genetic risk and other individual\u2010level covariates. Joint analysis of all contextual determinants indicated that more deleterious mixtures of contextual determinants are associated with lower late\u2010life cognition among apolipoprotein E \u025b4 non\u2010carriers with intermediate polygenic risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Contextual determinants are associated with dementia and late\u2010life cognition after adjusting for age, sex, education, and genetic risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71384","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:16:29Z","timestamp":1776334589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating contextual determinants and polygenic risk to examine dementia and late\u2010life cognition in the Multi\u2010Ethnic Study of Atherosclerosis"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-2253","authenticated-orcid":false,"given":"Diane","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Genetics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana A.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Urban Health Collaborative and Department of Epidemiology and Biostatistics, Dornsife School of Public Health Drexel University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilah","family":"Besser","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Brain Health, Department of Neurology University of Miami  Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of 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